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Acute-Phase Proteins and Mortality in Status Epilepticus: A 5-Year Observational Cohort Study

Sutter, Raoul MD1,2,3; Grize, Leticia PhD4; Fuhr, Peter MD2; Rüegg, Stephan MD2; Marsch, Stephan MD, PhD1

doi: 10.1097/CCM.0b013e318287f2ac
Clinical Investigations

Objective: Acute-phase proteins, such as C-reactive protein and albumin, may be related with course and outcome in status epilepticus, as changes of cytokine levels and blood-brain barrier breakdown during status epilepticus have been demonstrated. The aim of this study was to elucidate the association of C-reactive protein and albumin with course and outcome of status epilepticus.

Design: Observational cohort study.

Setting: This study was performed on the ICU of a university-affiliated tertiary care center.

Patients: All consecutive patients with status epilepticus from 2005 to 2009 were selected from a prospectively established electroencephalography database.

Intervention None.

Measurements: Albumin was assessed at admission and status epilepticus onset, and C-reactive protein was assessed during the first 3 days of status epilepticus. Outcomes were defined as refractory status epilepticus and death.

Main Results: One hundred thirty-five consecutive status epilepticus patients were analyzed. Patients with higher levels of albumin at status epilepticus onset had significant lower odds for the development of refractory status epilepticus and death (with every 1g/L: odds ratio 0.91, 95% confidence interval 0.86–0.96, p = 0.001; odds ratio 0.88, 95% confidence interval 0.82–0.95, p < 0.0001, respectively). These associations remained significant after multiple adjustments for possible confounders and correction for multiple comparisons (with every 1g/L: odds ratio 0.92, 95% confidence interval 0.86–0.97, p = 0.004; odds ratio 0.87, 95% confidence interval 0.80–0.94, p = 0.001, respectively). Increased C-reactive protein levels at status epilepticus onset were associated with higher rates of refractory status epilepticus and death (with every 1mg/L: odds ratio 1.01, 95% confidence interval 1.00–1.02, p = 0.021; odds ratio 1.01, 95% confidence interval 1.00–1.02, p < 0.007, respectively). These associations were inconsistent after adjustment for possible confounders and corrections for multiple comparisons (with every 1mg/L: odds ratio 1.01, 95% confidence interval 1.00–1.02, p = 0.109; odds ratio 1.01, 95% confidence interval 1.00–1.02, p = 0.043).

Conclusions: Albumin levels measured early in status epilepticus are independently associated with refractory epileptic activity and death while C-reactive protein levels were inconsistent. Further studies are needed to assess the potential of acute-phase proteins for inclusion in prediction models allowing to identify patients with poor outcome of status epilepticus.

1 Clinic of Intensive Care Medicine, University Hospital Basel, Basel, Switzerland.

2 Division of Clinical Neurophysiology, Department of Neurology, University Hospital Basel, Basel, Switzerland.

3 Division of Neurosciences Critical Care, Department of Anesthesiology, Critical Care Medicine and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.

4 Department of Epidemiology and Public Health, Public Health Institute and University of Basel, Basel, Switzerland.

This study was performed at Intensive Care Units, University Hospital Basel, Switzerland.

Dr. Sutter is supported by the Research Funds of the University of Basel, the Scientific Society Basel, and the Gottfried Julia Bangerter-Rhyner Foundation. Dr. Rüegg received unconditional research grants from UCB. He received honoraria from serving on the scientific advisory boards of Eisai and UCB, travel grants from GSK, Janssen-Cilag, UCB, and speaker fees from UCB and from serving as a consultant for Eisai, GlaxoSmithKline, Janssen-Cilag, Pfizer, Novartis, and UCB. He does not hold any stocks of any pharmaceutical industries or manufacturers of medical devices. The research of Dr. Fuhr is supported by the Swiss National Science Foundation, the Swiss Parkinson’s Disease Society, the Gossweiler Foundation, the Mach-Gaensslen Foundation, the Botnar Foundation, the Scientific Society Basel, the Novartis Foundation, Novartis, and Roche. He received honoraria from serving on the advisory boards of UCB and Abbott. The remaining authors have not disclosed any potential conflicts of interest.

The corresponding author had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. We confirm that all persons who contributed significantly to the work are listed as authors.

Current address for Dr. Sutter: Division of Neurosciences Critical Care, Department of ACCM, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Meyer 8–140, Baltimore, Maryland 21287. E-mail:

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© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins